Interferon-Gamma Increases the Immune Modulation of Umbilical Cord-Derived Mesenchymal Stem Cells but Decreases Their Chondrogenic Potential

The pro-inflammatory cytokine interferon-gamma (IFN-γ) is reported to be an agent that boosts the immune modulation of mesenchymal stem cells (MSCs). However, the effects of IFN-γ on the chondrogenic potential of treated MSCs have not been evaluated in depth. This study aimed to evaluate the effects of IFN-γ on the immune modulation and chondrogenic potential of human umbilical cord-derived MSCs (hUC-MSCs).UC-MSCs were isolated and expanded following published protocols. They were characterized as MSCs before their use in further experiments. The UC-MSCs were treated with IFN-γ at 10 ng/mL for 48 h. Changes in phenotype were investigated based on changes in MSC markers, immunomodulatory genes (TGF-β, IL-4, and IDO) for immune modulation, and cartilage-related genes during the induction of differentiation (Col1a2, Col2a1, Sox9, Runx2, and Acan) for chondrogenic potential.IFN-γ-treated UC-MSCs maintained MSC markers and exhibited decreased expression of transcriptional regulatory factors in chondrogenesis (Sox9 and Runx2) and the extracellular matrix-specific genes Col1a2 and Acan but not Col2a1 compared to non-treated cells (p < 0.05). Furthermore, the immunomodulatory capability of IFN-γ-treated UC-MSCs was clearly revealed through their increased expression of IDO and IL-4 and decreased expression of TGF-β compared to non-treated cells (p < 0.05).This study demonstrated that UC-MSCs treated with IFN-γ at 10 ng/mL had reduced expression of chondrocyte-specific genes; however, they maintained multi-lineage differentiation and exhibited immunomodulatory properties.